Cardiovascular disease remains one of the leading causes of mortality globally. Innovative techniques are required to tackle its anticipated rise due to rising obesity, diabetes and an ageing population. Personalised electronic coaching (eb coaching) using the Internet and emails may help motivate healthier living and be of clinical benefit in complementing current programmes for cardiovascular risk reduction. I investigated whether personalised ebcoaching on top of SOC was more clinically effective than SOC alone, in reducing cardiovascular risk in asymptomatic individuals with high cardiovascular risk. I lead a randomised controlled trial of 402 participants using robust surrogate markers to identify change over 6 months. I assessed the feasibility of using cardiovascular magnetic resonance surrogate markers to guide their use in future studies of lifestyle interventions. I performed systematic reviews to identify 1) similarities and differences among leading primary prevention guidelines that address cardiovascular screening and risk assessment and 2) guideline recommendations on lifestyle advice and interventions to identify how ebcoaching could be used and what advice to incorporate in ebcoaching platforms. I found modest but statistically significant improvements in both ebcoaching and SOC groups to a similar level. Personalised ebcoaching did not show additional benefit in a highbrisk primary prevention cohort. It is feasible to use cardiovascular surrogate markers derived from cardiovascular magnetic resonance in lifestyle interventions studies. However, further studies correlating change in these markers with longbterm outcomes are required. Considerable discrepancies exist in the guidelines on risk on cardiovascular screening and risk assessment, with no consensus on optimum screening strategies or classification of high risk thus affecting treatment threshold. Guidelines did highlight the importance of lifestyle interventions in primary prevention and generally provided similar advice. Ebcoaching should not be incorporated into current prevention programmes for high risk populations unless the tools are improved and effectiveness is proven.

Cardiovascular diseases are responsible for approximately a third of all death worldwide, with hypertension being a major risk factor for many of those. Hypertension can lead to left ventricle hypertrophy and diastolic and systolic dysfunction. Myocardial deformation parameters have been shown to have high sensitivity at the early stage of contractile dysfunction. They can be derived from myocardial tagging, considered to be the goldstandard method, or from routinely acquired cine images using feature tracking (FT) techniques. This work aimed to validate FT as a post processing technique. Three FT software packages were used to measure strain parameters in healthy subjects and hypertensive patients in order to assess agreement. Intra- and inter-observer reproducibility was also investigated. The CVI42 software was found to have the best reproducibility. Good agreement across the three software packages and both groups was also observed for circumferential strain calculated from mid-ventricle short axis and longitudinal strain parameters. CVI42 was also compared to the reference tagging analysis by applying both techniques to a healthy and hypertensive patient cohort. Although tagging could discriminate between the two populations (longitudinal strain), no statistically significant differences were found by CVI42. The final validation step was to generate simulation models mimicking simplified cardiac views to compare the experimental results against a true gold-standard for which strain values are known. Two commercial FT software packages were used to analyze the simulated cine images with increasing complexity levels. Both showed inaccurate tracking and high errors compared to analytical values. This indicated that more realistic and complex numerical models should be investigated. Although FT is a relatively new and promising technique, the results demonstrated that it still requires going through standardization to better understand inter-vendor variability.

Marfan Syndrome leads to the weakening of the thoracic aorta and ultimate rupture causing death of the patient. Current monitoring method involves measuring the diameter of the aorta near the heart. Our approach is to develop a new technology that will provide clinicians the ability to evaluate the size, shape and motion of the entire thoracic aorta using four-dimensional cardiac MRI. This project alters the existing research algorithms to provides an integrated application for processing the images and provides novel measurements about the aorta from a data set of 32 normal subjects and 38 patients with serial scans.

Pulmonary arterial hypertension (PAH) alters pulmonary hemodynamics by changing the vascular wall mechanics. Currently, pulmonary vascular resistance is used clinically to assess the disease. However, the invasive nature of pressure measurements, needed for calculating the resistance, prevents longitudinal monitoring of patients during therapy. This work employs wave reflection as an alternative measure of the downstream stiffness and proposes a new method for wave reflection assessment using only non-invasive phase contrast magnetic resonance (PCMR) flow data. The feasibility of the proposed method was investigated in a numerical model of blood flow in the right pulmonary artery. Furthermore, it was validated experimentally using a flow phantom and compared with an existing invasive technique. Finally, the feasibility of the method was tested in a study of the right pulmonary artery of a volunteer. This approach may provide a non-invasive method to evaluate PAH and its response to therapy.

Pulmonary arterial hypertension (PAH) alters pulmonary hemodynamics by changing the vascular wall mechanics. Currently, pulmonary vascular resistance is used clinically to assess the disease. However, the invasive nature of pressure measurements, needed for calculating the resistance, prevents longitudinal monitoring of patients during therapy. This work employs wave reflection as an alternative measure of the downstream stiffness and proposes a new method for wave reflection assessment using only non-invasive phase contrast magnetic resonance (PCMR) flow data. The feasibility of the proposed method was investigated in a numerical model of blood flow in the right pulmonary artery. Furthermore, it was validated experimentally using a flow phantom and compared with an existing invasive technique. Finally, the feasibility of the method was tested in a study of the right pulmonary artery of a volunteer. This approach may provide a non-invasive method to evaluate PAH and its response to therapy.

Purpose: To evaluate the diagnostic performance of Coronary Computed Tomography Angiography (CCTA) in predicting Myocardial Perfusion Scintigraphy (MPS) perfusion defects in low likelihood patients with End Stage Renal Disease (ESRD) awaiting transplant. Materials and Methods: In total, 131 consecutive patients with ESRD awaiting transplant were prospectively enrolled in this study (86 men; 54±9years). All patients underwent MPS as per standard of care and in addition non-enhanced CT for calcium scoring (CAC score) and Coronary Computed Tomography Angiography (CCTA). Results: The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CAC score in predicting MPS perfusion defects were 88%, 35%, 28% and 92%, respectively. The sensitivity, specificity, PPV and NPV of CCTA in predicting MPS perfusion defects at the patient level were 55%, 87%, 57% and 87%, respectively, and 48%, 92%, 41% and 94% at the vessel level. The diagnostic performance of CCTA in predicting MPS perfusion defects improved when patients with CAC score higher than 1000 (15/70, 21%) were excluded from the analysis. In patients with positive CAC score up to 1000 sensitivity, specificity, PPV and NPV at the patient level were 60%, 93%, 75% and 86% respectively. These were 53%, 91%, 36% and 95%, respectively, at the vessel level. Conclusion: Non-enhanced CT for CAC score and CCTA can be considered useful diagnostic tools in the ESRD population, particularly in identifying patients without coronary artery disease. This approach however had limitations in the presence of high CAC score.

No description available.

The non-invasive cardiovascular imaging modalities, cardiovascular magnetic resonance (CMR) and multi-detector computer tomography (MDCT) are playing an increasing role in both clinical and research settings. CMR is a unique imaging modality due to unsurpassed contrast between soft tissue structures that is non-invasive, does not use ionising radiation and is able to provide high-resolution information about cardiac anatomy, function, flow, perfusion, viability and metabolism. It has provided the gold standard in imaging in congenital heart disease. Recent advances in this technology have led to images of high spatial and temporal resolution that has made the characterisation of atheroma possible. While currently spatial resolution still limits its ability to characterise atheroma in native human coronary arteries in living patients, CMR imaging of the coronary arteries has future potential with further technological and sequence advances. MDCT has been used in clinical settings to measure of the amount of calcification in the coronary arteries with “coronary artery calcium scoring” of the coronary tree a surrogate marker of atherosclerosis. MDCT has also become the gold standard for angiographic imaging in most arterial beds such as the carotid and peripheral vascular systems. In the coronary arteries in particular, there have been major advances in the accuracy of coronary MDCT angiography, particularly with regards to its negative predictive value, although excessive calcification and blooming artefacts still limit the diagnostic accuracy of the technique for assessing stenotic severity. In this thesis, our aims were to address some specific novel areas advancing the utility of these imaging modalities in two major areas of interest, namely congenital heart disease and atheroma imaging. Our first step was to validate the accuracy and reproducibility of CMR, the main imaging modality we utilised. To achieve this, we assessed MR imaging of cardiac volumes and function in a normal adult Australian population with a specific focus on the reproducibility of the technique. In confirming that this technique in our hands is both accurate and reproducible, we would then be in a position to be able to confidently use this technique in our future chapters. However, more than this, we sought to establish some normal ranges for left and right atrial and ventricular parameters in our local population. This would be crucial background information for us to be able to make comparisons with future studies in patients with congenital heart disease. Having established our technique and reference ranges, we would then explore the two specific issues in the ensuing two chapters using CMR in one area of congenital heart disease, atrial septal defect. Atrial septal defect is the most common congenital heart defect first diagnosed in adults. The traditional method of assessment of these patients and for suitability for ASD closure involves semiinvasive investigation with transoesophageal echocardiography (TOE) for measurement of the defect size and atrial septal margins. MRI assessment of patients prior to percutaneous device closure compared to TOE assessment would provide information on the accuracy of TOE assessment and provide information of the utility of cardiac MRI as an alternative to TOE for the work-up of these patients prior to ASD closure. In our third original research chapter, we utilised CMR to understand the effects of percutaneous ASD closure on cardiac chamber volumes. We achieved this by assessing with cardiac MRI pre-closure and post-closure atrial and ventricular cardiac volumes. Longstanding right heart dilatation in the setting of an ASD may lead to complications including right heart failure, pulmonary hypertension and arrhythmia. Closure of the ASD should reduce right heart volumes by removing left-to-right shunting and lead to normalisation of ventricular volumes. The assessment of atrial volume changes with ASD closure may be important in furthering our understanding in its contribution to arrhythmia. Having assessed the ability of CMR to assess both the ASD dimensions, and therefore suitability for percutaneous closure, as well as the effects of ASD closure on cardiac chamber size, we look in the final two original research chapters to move to another area of research development with these highresolution imaging technologies, atherosclerosis imaging. Two particular areas we wished to focus on included the potential of high-resolution MR imaging to monitor effects of HDL infusion on atherosclerosis, and secondly to explore mechanisms behind limitations in MDCT imaging of atherosclerosis, specifically calcification and blooming artifacts. For assessing the effects of HDL infusion on atherosclerosis, we utilised a cholesterol-fed rabbit model of atherosclerosis. The abdominal aorta of the rabbit is comparable in size to the human coronary artery. Previous work with the rabbit model of atherosclerosis and magnetic resonance imaging of the aortic wall has shown that it can provide information about atherosclerotic composition as well as provide serial data of the arterial wall. While high intensity lipid-lowering with statins remains the first line management of at risk individuals, modest manipulations of serum HDL levels are associated with a significant impact on cardiovascular risk. Thus, we assessed the effect of HDL infusion and atorvastatin in a rabbit model of using MRI aortic atherosclerosis as the endpoint. In our fifth and final original research chapter, we assessed the accuracy of quantification of atherosclerotic calcification with MDCT in the carotid arteries of patients undergoing carotid endarterectomy, and sought to identify algorithms or techniques that may improve quantification of calcification. This would potentially lead to an improvement in the ability of MDCT techniques to quantify stenotic severity in coronary arteries that were calcified. To achieve these we utilised MDCT in vivo and in comparison with carotid endarterectomy specimen micro-CT. Importantly, as part of this study, we undertook a thorough assessment of reproducibility of these techniques. Thus, in summary, we have been able to confirm the accuracy and reproducibility of CMR and MDCT in the areas of a specific congenital defect (ASD) and atherosclerosis imaging, and utilised these techniques to advance our understanding of these disease states. This thesis identifies strengths and weaknesses of these techniques that will allow us to more appropriately use them for future purposes in cardiovascular disease. Future work directly stemming from this thesis has already begun, and now looks to address issues of whether CMR and MDCT may provide complimentary information about atherosclerotic lesions that may benefit outcomes in certain conditions. Specifically the work in this thesis has led to studies commencing in carotid atherosclerosis and saphenous vein graft atherosclerosis and using these imaging techniques to potentially predict adverse future outcomes. / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2008

The non-invasive cardiovascular imaging modalities, cardiovascular magnetic resonance (CMR) and multi-detector computer tomography (MDCT) are playing an increasing role in both clinical and research settings. CMR is a unique imaging modality due to unsurpassed contrast between soft tissue structures that is non-invasive, does not use ionising radiation and is able to provide high-resolution information about cardiac anatomy, function, flow, perfusion, viability and metabolism. It has provided the gold standard in imaging in congenital heart disease. Recent advances in this technology have led to images of high spatial and temporal resolution that has made the characterisation of atheroma possible. While currently spatial resolution still limits its ability to characterise atheroma in native human coronary arteries in living patients, CMR imaging of the coronary arteries has future potential with further technological and sequence advances. MDCT has been used in clinical settings to measure of the amount of calcification in the coronary arteries with “coronary artery calcium scoring” of the coronary tree a surrogate marker of atherosclerosis. MDCT has also become the gold standard for angiographic imaging in most arterial beds such as the carotid and peripheral vascular systems. In the coronary arteries in particular, there have been major advances in the accuracy of coronary MDCT angiography, particularly with regards to its negative predictive value, although excessive calcification and blooming artefacts still limit the diagnostic accuracy of the technique for assessing stenotic severity. In this thesis, our aims were to address some specific novel areas advancing the utility of these imaging modalities in two major areas of interest, namely congenital heart disease and atheroma imaging. Our first step was to validate the accuracy and reproducibility of CMR, the main imaging modality we utilised. To achieve this, we assessed MR imaging of cardiac volumes and function in a normal adult Australian population with a specific focus on the reproducibility of the technique. In confirming that this technique in our hands is both accurate and reproducible, we would then be in a position to be able to confidently use this technique in our future chapters. However, more than this, we sought to establish some normal ranges for left and right atrial and ventricular parameters in our local population. This would be crucial background information for us to be able to make comparisons with future studies in patients with congenital heart disease. Having established our technique and reference ranges, we would then explore the two specific issues in the ensuing two chapters using CMR in one area of congenital heart disease, atrial septal defect. Atrial septal defect is the most common congenital heart defect first diagnosed in adults. The traditional method of assessment of these patients and for suitability for ASD closure involves semiinvasive investigation with transoesophageal echocardiography (TOE) for measurement of the defect size and atrial septal margins. MRI assessment of patients prior to percutaneous device closure compared to TOE assessment would provide information on the accuracy of TOE assessment and provide information of the utility of cardiac MRI as an alternative to TOE for the work-up of these patients prior to ASD closure. In our third original research chapter, we utilised CMR to understand the effects of percutaneous ASD closure on cardiac chamber volumes. We achieved this by assessing with cardiac MRI pre-closure and post-closure atrial and ventricular cardiac volumes. Longstanding right heart dilatation in the setting of an ASD may lead to complications including right heart failure, pulmonary hypertension and arrhythmia. Closure of the ASD should reduce right heart volumes by removing left-to-right shunting and lead to normalisation of ventricular volumes. The assessment of atrial volume changes with ASD closure may be important in furthering our understanding in its contribution to arrhythmia. Having assessed the ability of CMR to assess both the ASD dimensions, and therefore suitability for percutaneous closure, as well as the effects of ASD closure on cardiac chamber size, we look in the final two original research chapters to move to another area of research development with these highresolution imaging technologies, atherosclerosis imaging. Two particular areas we wished to focus on included the potential of high-resolution MR imaging to monitor effects of HDL infusion on atherosclerosis, and secondly to explore mechanisms behind limitations in MDCT imaging of atherosclerosis, specifically calcification and blooming artifacts. For assessing the effects of HDL infusion on atherosclerosis, we utilised a cholesterol-fed rabbit model of atherosclerosis. The abdominal aorta of the rabbit is comparable in size to the human coronary artery. Previous work with the rabbit model of atherosclerosis and magnetic resonance imaging of the aortic wall has shown that it can provide information about atherosclerotic composition as well as provide serial data of the arterial wall. While high intensity lipid-lowering with statins remains the first line management of at risk individuals, modest manipulations of serum HDL levels are associated with a significant impact on cardiovascular risk. Thus, we assessed the effect of HDL infusion and atorvastatin in a rabbit model of using MRI aortic atherosclerosis as the endpoint. In our fifth and final original research chapter, we assessed the accuracy of quantification of atherosclerotic calcification with MDCT in the carotid arteries of patients undergoing carotid endarterectomy, and sought to identify algorithms or techniques that may improve quantification of calcification. This would potentially lead to an improvement in the ability of MDCT techniques to quantify stenotic severity in coronary arteries that were calcified. To achieve these we utilised MDCT in vivo and in comparison with carotid endarterectomy specimen micro-CT. Importantly, as part of this study, we undertook a thorough assessment of reproducibility of these techniques. Thus, in summary, we have been able to confirm the accuracy and reproducibility of CMR and MDCT in the areas of a specific congenital defect (ASD) and atherosclerosis imaging, and utilised these techniques to advance our understanding of these disease states. This thesis identifies strengths and weaknesses of these techniques that will allow us to more appropriately use them for future purposes in cardiovascular disease. Future work directly stemming from this thesis has already begun, and now looks to address issues of whether CMR and MDCT may provide complimentary information about atherosclerotic lesions that may benefit outcomes in certain conditions. Specifically the work in this thesis has led to studies commencing in carotid atherosclerosis and saphenous vein graft atherosclerosis and using these imaging techniques to potentially predict adverse future outcomes. / Thesis (Ph.D.) -- University of Adelaide, School of Medical Sciences, 2008

A intervenção percutânea com implante de stents constitui-se na principal forma de revascularização miocárdica empregada, e associa-se à redução de sintomas, à melhoria na qualidade de vida e ao aumento da sobrevida em pacientes acometidos por síndrome coronária aguda. Entretanto, o implante de stents pode acompanhar-se de exagerada hiperplasia intimal, principal determinante da reestenose destes dispositivos. Diversos fatores clínicos, anatômicos e técnicos associam-se a maiores taxas de reestenose, porém a hipótese de que o tipo ou a composição da lesão aterosclerótica tratada possa correlacionar-se com o fenômeno ainda não foi esclarecida. Determinar a relação entre a composição da placa aterosclerótica tratada conforme análise pela Histologia Virtual® - e a magnitude da hiperplasia intimal após o implante de stents farmacológicos e não-farmacológicos. No período de setembro de 2008 a novembro de 2009, selecionamos 52 pacientes prospectivos com o diagnóstico de síndrome coronária aguda com ou sem supra ST, submetidos à cinecoronariografia e candidatos à intervenção percutânea. Estes foram randomizados para o tratamento com stents farmacológicos com sirolimus (Cypher® Cordis, Johnson & Johnson) ou com stents não-farmacológicos (Driver®,Medtronic Inc.). O ultra-som com Histologia Virtual® foi realizado antes do tratamento das lesões culpadas, e correlacionou-se o porcentual dos componentes fibrótico, fibrolipídico, núcleo necrótico e cálcio com o grau de hiperplasia intimal, em reestudo ultrasonográfico realizado aos 9 meses. A média de idades foi de 55,3 anos (DP 4,9 anos), sendo 77% homens. Não foram verificadas diferenças significativas entre os grupos no que se refere às variáveis clínicas e angiográficas. A maioria dos pacientes apresentava obstrução coronária uniarterial, e o vaso mais freqüentemente tratado foi a descendente anterior. À Histologia Virtual®, não foram detectadas diferenças em relação ao tipo de placa tratada, sendo predominantes as lesões do tipo fibroateroma e fibroateroma calcificado. O tecido fibrótico foi o componente preponderante [59,6% (DP 15,8%) do volume total das placas analisadas], e cerca de 20% do volume das lesões era composto por núcleo necrótico. Após 9 meses, o reestudo ultrasonográfico foi realizado em 49 (94%) dos pacientes. Tanto o volume como o porcentual de hiperplasia intimal foram significativamente maiores no grupo tratado com stents não-farmacológicos [60,8 mm3 [DP 32 mm3] versus 14 mm3 (DP 9,2 mm3), p<0,0001 e [31,9% (DP 12,9%) versus 8,2% (DP 7,6%) , p<0,0001, respectivamente]. Contudo, não foi observada associação entre os porcentuais dos componentes fibrótico (corr. 0,038, p=0,81), fibrolipídico (corr. 0,109, p=0,49), cálcio (corr. -0,073, p=0,64) e núcleo necrótico (corr. -0,062, p=0,69) das lesões tratadas com o tecido neointimal intra-stent. Os resultados desta investigação prospectiva e randomizada indicam que as informações providas pela Histologia Virtual® na caracterização das placas ateroscleróticas não auxiliam na identificação de lesões mais propensas à reestenose, após o implante de stents farmacológicos e não-farmacológicos. / To the present, little is known about the correlation between modifications in plaque composition at stent edges and the changes in vessel geometry. This study sought to evaluate, by serial grey-scale intravascular ultrasound (IVUS) and Virtual Histology(TM), the modifications in plaque composition at the edges of drug-eluting and bare-metal stents and the correlation of these findings with changes in the measuremntes of vessel, lumen and plaque area at those segments. Single-center, prospective and randomized (1:1) evaluation of 40 patients with acute coronary syndrome treated with bare-metal (Driver(TM), n=20 patients) or drug-eluting stents (Cypher(TM), n=20 patients). Following stent deployment, all individuals underwent gray scale IVUS and Virtual Histology(TM) evaluation, which were repeated at nine months. Primary endpoint included the modification in vessel, lumen and plaque area and in the composition of the plaque in the mean time between the baseline and follow-up procedure. Additionally, we tried to determine a correlation between plaque composition variation and changes in vessel geometry. At the proximal edge of both drug-eluting and bare-metal stents there was a trend to positive vessel remodeling which compensated the modest increase in plaque area. At the distal edge, patients treated with drug-eluting stents had less plaque growth resulting in a larger lumen area at follow-up. By Virtual Histology, there was a marked reduction in the % of fibrotic tissue and necrotic core in both edges of the two stents and a positive, strong correlation was seen between increase in % of fibrofatty component and augmentation in plaque area(r=0.78, p=0.01). The use of drug-eluting stents was not associated with \"edge effect\". On the contrary, patients treated with these devices experienced less plaque growth, especially at the distal edge of the stents. Modifications in plaque composition, with increase in fibrofatty content, might partially explain these findings.